rs8008724
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004094.5(EIF2S1):c.474-158T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Consequence
EIF2S1
NM_004094.5 intron
NM_004094.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.156
Genes affected
EIF2S1 (HGNC:3265): (eukaryotic translation initiation factor 2 subunit alpha) The translation initiation factor EIF2 catalyzes the first regulated step of protein synthesis initiation, promoting the binding of the initiator tRNA to 40S ribosomal subunits. Binding occurs as a ternary complex of methionyl-tRNA, EIF2, and GTP. EIF2 is composed of 3 nonidentical subunits, the 36-kD EIF2-alpha subunit (EIF2S1), the 38-kD EIF2-beta subunit (EIF2S2; MIM 603908), and the 52-kD EIF2-gamma subunit (EIF2S3; MIM 300161). The rate of formation of the ternary complex is modulated by the phosphorylation state of EIF2-alpha (Ernst et al., 1987 [PubMed 2948954]).[supplied by OMIM, Feb 2010]
GPHN (HGNC:15465): (gephyrin) This gene encodes a neuronal assembly protein that anchors inhibitory neurotransmitter receptors to the postsynaptic cytoskeleton via high affinity binding to a receptor subunit domain and tubulin dimers. In nonneuronal tissues, the encoded protein is also required for molybdenum cofactor biosynthesis. Mutations in this gene may be associated with the neurological condition hyperplexia and also lead to molybdenum cofactor deficiency. Numerous alternatively spliced transcript variants encoding different isoforms have been described; however, the full-length nature of all transcript variants is not currently known. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EIF2S1 | NM_004094.5 | c.474-158T>A | intron_variant | ENST00000256383.11 | NP_004085.1 | |||
GPHN | XM_047430879.1 | c.1312+321715T>A | intron_variant | XP_047286835.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EIF2S1 | ENST00000256383.11 | c.474-158T>A | intron_variant | 1 | NM_004094.5 | ENSP00000256383.4 | ||||
EIF2S1 | ENST00000466499.6 | c.474-158T>A | intron_variant | 1 | ENSP00000425299.1 | |||||
EIF2S1 | ENST00000557310.5 | c.474-158T>A | intron_variant | 2 | ENSP00000451975.1 | |||||
EIF2S1 | ENST00000555876.1 | c.342-158T>A | intron_variant | 2 | ENSP00000452034.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152096Hom.: 0 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152096Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74312
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at